Transdermal Systems for the Delivery of Ionic Agents Directly to Open Wounds and Surgically Repaired Incisions

ABSTRACT

A transdermal system for the delivery of an anesthetic or other active therapeutic agent directly to a selected site of injured skin tissue by iontophoresis is disclosed, which utilizes a transdermal skin-worn patch including a donor electrode chamber containing a donor electrode and an amount of an active agent in a form suitable for transdermal delivery in electrical communication with the donor electrode and a return electrode. The patch also contains a source of electric current connected in a circuit with the donor and return electrode, a current regulating device is optionally provided in the circuit for controlling the electrical output of the patch and at least the donor electrode chamber includes a provision for absorbing a quantity of fluid associated with weepage from adjacent injured skin tissue.

CROSS-REFERENCED TO RELATED APPLICATIONS

This application is a non-provisional application claiming the benefitof U.S. Provisional Application Ser. No. 60/865,471, filed Nov. 13, 2006and which is deemed incorporated by reference herein in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable

BACKGROUND OF THE INVENTION

I. Field of the Invention

The present invention is related generally to transdermal delivery ofionic agents and, more particularly, to the transdermal delivery oflocal anesthetic agents directly into repaired incisions and skin woundsfor the management of pain by the use of an applied electro-motive force(emf), commonly known as iontophoresis.

II. Related Art

The process of iontophoresis was described by LeDuc in 1908 and hassince found commercial use in the delivery of ionically chargedtherapeutic agent molecules such as pilocarpine, lidocaine anddexamethasone. In this delivery method, ions bearing a positive chargeare driven across the skin at the site of an electrolytic electricalsystem anode while ions bearing a negative charge are driven across theskin at the site of an electrolytic system cathode.

Earlier, and some present, iontophoretic devices have been typicallyconstructed of two electrodes attached by adhesive materials to apatient, each connected by a wire to a remote power supply, generally amicroprocessor-controlled electrical instrument. More recently,self-contained wearable iontophoretic systems have been developed. Thesesystems are advantageous in that they do not have external wires and aremuch smaller in size. Examples of such systems can be found in a varietyof U.S. patents, including U.S. Pat. Nos. 4,927,408; 5,358,483;5,458,569; 5,466,217; 5,533,971; 5,605,536; 5,651,768; 5,685,837;6,421,561; 6,653,014; and 6,745,071. Other examples of wearable systemscan be found in patent application publications 2005/0010161;2005/0015042 and 2004/0267169. These systems are also comprised of twoelectrodes fixed to patients by means of adhesive materials.

Iontophoretic devices have been used for the delivery of anestheticagents, in order to create a numbing effect in normal intact skin, toprophylactically minimize pain associated with needlestick insertion orminor surgical procedures. Research has demonstrated that this can be aneffective treatment, as exemplified, for example, in a research articleby Russo et al. (Lidocaine Anesthesia: Comparison of Iontophoresis,Injection, and Swabbing, Am. J. Hosp Pharm, 1980, 37:843-847). The Russoarticle concludes that iontophoresis of lidocaine through intact skin asa prophylactic treatment for skin anesthesia, is more effective thantopical delivery. A commercially available product for this purpose isNumby Stuff®, sold by Iomed Inc. A similar product, LidoSite® is sold byVyteris, Inc.

These prior art devices are limited to prophylactic treatment of intactskin, using a short application duration of approximately 10-20 minutes,and current levels averaging at approximately 2-4 mA, to achievesufficient delivery of anesthetic agent to numb skin in areas ofapproximately 7-8 cm² (i.e., using current densities of 250-600microamps/cm²). Ironically, these higher current levels can themselvesserve to cause pain that is intended to be avoided.

The efficiency in which ions are transferred into the body byiontophoresis is much lower than 100%, and is dependent on severalfactors. For best efficiency, the species to be delivered will carry acharge, so that it will flow in the electric field. Also important formaximum efficiency is to minimize competing ions, which are ions ofsimilar charge to the species desired to be transferred. Competing ionspresent along with the desired delivery species will lower deliveryefficiency, by a proportion related to the relative concentration andsize of the competing ions. Also serving to reduce delivery efficiencyis ions of opposite charge present in the body, which transfer back tothe delivery chamber as a proportion of total charge flow. Theseefficiency effects are known in the art and published in articles suchas Phipps et al, Iontophoretic Delivery of Model Inorganic and DrugIons, J. Pharm Sci., Vol. 78, No. 5, May 1989, pp 365-369. Even underoptimal conditions, delivery efficiency is less than 50%. For positivelycharged drugs of molecular weight 181-260 daltons, efficiency can be4.2-23.9%. When there is poor efficiency, current levels must be veryhigh to sustain the desired delivery rate. This is problematic in thathigh current rates are associated with skin damage.

Traditionally, skin wounds and surgically repaired incisions have beentreated with oral medication, and/or localized injections. Limitationsassociated with oral medications include the stomach discomfortassociated with NSAIDS, a non-constant pain management owing to the “upsand downs” of blood levels after oral ingestions, and the dangers ofaddition and respiratory depression associated with narcotics.Limitations associated with local injections of anesthetic agentsinclude the pain associated with the injection itself, as well as ashort duration of action related with the eventual migration ofmedication away from the treatment site.

Other approaches to treat incision and wound pain for protracted periodsinclude mechanical delivery of anesthetic fluids through implantedcatheters. This technique suffers from the costly and invasive nature ofusing implantable catheters. Another approach is to utilize topicallyapplied passive patches, as described in U.S. Pat. Nos. 6,383,511 and6,645,521. This approach suffers from a slow onset of action related topassive delivery.

Little is known about iontophoretic delivery into wounds, particularlyfresh wounds where blood or interstitial fluid will weep into theiontophoretic delivery chamber. These fluids will carry both competingions of like charge into the delivery chamber, and counter ions ofopposite charge. Both serve to interfere with and significantly affectdelivery efficiency in an adverse manner. Thus, either much highercurrent levels would be necessary to overcome the affects of competingions, or effective delivery may not be possible at all.

As indicated, an example of prior art current and current density withregard to intact skin can be derived from the published study by Russoet al (above). In this article, a charge dosage of approximately 4 mAmin per square cm provided a skin anesthesia which lasted approximately25 minutes in a skin area of 7 cm². Therefore, this art would suggestthat 0.16 mA per sq. cm would be sufficient at a constant rate overintact skin. Therefore, it would be expected that a wound care deliverysystem would require a much greater current density given anunrestricted path for back-flow of counter ions, which would dominatethe total current flow. Thus, because of the interference of competingions and increased sensitivity to current levels associated with injuredskin, direct application of ionic agents should not be a viableapproach.

To date, no commercial iontophoretic products exist for sustaineddelivery of anesthetic agents in order to manage pain following aninjury such as a skin wound or surgically repaired incision. U.S. Pat.No. 6,560,483 describes an iontophoretic delivery patch for thesustained treatment of an epidermal target site in the form of a borderportion patch that surrounds an aperture region which may contain anincision or skin wound. No contact occurs between the delivery patch andskin at the site of the incision or wound. The effectiveness of thatdevice depends on the lateral movement of medication to the openaperture region, where an incision or skin wound may exist, otherwisethe site of pain itself is not treated directly. The limitations of thisapproach include: a high delivery current that would be required tosupply enough medication to treat laterally adjacent tissue, and arelatively slow onset of action associated with the time it takes for alateral transfer of medication to take place. As mentioned previously,the use of high currents is undesirable as skin damage may occur andthat can be self-defeating in the administration of pain medications.

Therefore, a need exists for a better means to treat incisions andwounds that is non-invasive, includes sustained release of medicationwith rapid onset of action and is comfortable to wear.

SUMMARY OF THE INVENTION

In accordance with the present invention, it has been discovered thatactive agents, particularly local anesthetic agents can be successfullyand safely applied directly to repaired incision or other skin wouldsites using iontophoresis techniques. Applications can be successful forrelatively long periods of time.

Contrary to previous teachings and indications regarding iontophoresispatches covering wounds or incisions, applicants have discovered thatthe current can actually be reduced to safe levels for injured skinwhile successfully maintaining a desired agent dosage. Current densitiespreferably range from about 0.005 to ≦0.15 mA/cm². Current densities arepreferably <0.10 mA/cm² and most preferable are below 0.05 mA/cm².

The present invention provides a system for the direct application ofanesthetic agents by iontophoresis for the treatment of concurrent painassociated with skin incisions and wounds. While many compounds may beuseful with the invention, as will be discussed below, it isparticularly useful for the delivery of anesthetic agents such aslidocaine, bupivicaine, ropivicaine, and mepivicaine to damaged skin.

The system features a patch device with a donor or delivery chamber thatis designed to be applied directly over the incision or wound site andutilizes an electric field to stimulate delivery of the anestheticagent(s) with a rapid onset of action. The patch is sterilized so thatrisk of infection is minimal. Additionally, the system deliversmedication in a constant manner over an extended period of time.Generally, such time periods are at least 30 minutes and may extend toas many as 96 hours.

Importantly, current (and current densities) with the system of thepresent invention are maintained at very low levels when compared withknown devices, so that sufficient pain reduction is achieved atcomfortable levels of current. In this regard, it has been found thatthe relatively higher total currents and current densities traditionallyutilized for skin anesthesia are unacceptable when used over wounds andskin incisions.

According to one aspect, patches of the present invention alsoincorporate additional features to allow them to absorb excess fluidassociated with weepage from an adjacent incision, wound or otherlesion. The anesthetic or other active material is contained in anabsorbent medium that also has the ability to absorb weepage fluid. Suchmaterial may be selected from any natural or synthetic fibrous materialsthat are inert to or do not react with or interfere with the delivery ofthe anesthetic material and are not affected by weepage fluid. Suchmaterials may include cellulose and polypropylene fibers, for example.The anesthetic or other active material itself may be contained in awater solution or in a gelled form, for example, as a viscous solutionin hydroxypropylmethylcellulose (HPMC).

Illustrative embodiments include two approaches to manage the weepagefrom a wound: fixed volume and variable volume. The fixed volumeapproach is a design that incorporates an iontophoretic delivery chamberhaving a volume that includes unused absorption capacity that does notappreciably change over time. In contrast, the variable volume approachincorporates an iontophoretic delivery chamber that is capable ofexpanding to absorb fluid material.

One fixed volume approach comprises a delivery pad that is underfilled(or undersaturated), and therefore capable of absorbing excess fluid.This can be accomplished as by providing a delivery pad which isunderfilled as illustrated in FIG. 2 a. Alternatively, more elaboratemeans can be utilized with this approach. For example, an expansionvolume space of fixed dimensions and unused absorption capacity can beconnected to the delivery chamber, as shown by FIG. 2 b.

The expansion volume approach for accepting weepage utilizes aniontophoretic delivery chamber capable of expanding or stretching. Thiscan be accomplished using stretchable materials in a delivery chamber asillustrated in FIG. 3. Alternatively, non-stretchable materialsconfigured to shift or accordion or expand in a fan-like (or similar)manner will also serve to expand the chamber to accommodate weepage.

Other embodiments may be used to administer other types of active agentssuch as ionic anti-microbial compounds or even non-ionic compoundsthrough electro-osmosis. One illustrated embodiment is used for thetreatment of acne lesions.

BRIEF DESCRIPTION OF THE DRAWINGS

In the figures wherein like reference characters depict like parts:

FIG. 1 is a schematic representation showing a top view of a patch (withinternal components) usable for the transdermal delivery of anestheticagents in accordance with the invention;

FIG. 2 a is a schematic representation showing a section through adelivery pad as it appears attached to the skin of a patient which isunderfilled to enable acceptance of weepage volume from an incision orwound;

FIG. 2 b is a schematic sectional view similar to FIG. 2 a throughanother embodiment of a delivery pad which includes a separateunsaturated portion of the delivery chamber to accept weepage volume;

FIG. 3 depicts a sectional schematic view similar to FIG. 2 a of yetanother embodiment of a delivery pad which includes stretchable chamberwalls;

FIG. 4 shows a representation of lidocaine microdialygate levels in theskin represented by plots of lidocaine concentration levels versus timefor both active and passive linear probes placed under or next to asurgical incision;

FIG. 5 depicts a comparison of lidocaine penetration in both passive andactive (0.15 mA/cm² current) patches using plots of concentration versustime; and

FIG. 6 depicts a top view schematic representation (with internalcomponents) of an acne treatment patch.

DETAILED DESCRIPTION

The detailed description that follows involves a description of certainembodiments which are presented as examples representing the novelconcepts of the present invention rather than as limitations on thescope of any of these concepts.

FIG. 1 depicts a schematic top view of an iontophoretic patch devicesuitable for the transdermal delivery of anesthetic agents in accordancewith the invention. The patch, represented generally by the referencecharacter 10, is shown with internal parts exposed and includes a donoror delivery electrode Chamber 12 containing an absorbent pad 13 whichincludes an amount of an anesthetic agent to be delivered and a donor ordelivery electrode shown at 14. The donor electrode chamber contains theactive anesthetic agent to be delivered transdermally and is designed toCover an incision or other wound together with an amount of thesurrounding skin providing a fixed and known designated contact area.While the donor electrode chamber of FIG. 1 is shown as an elongated,generally rectangular shape, it will be appreciated that any convenientshape of known area may be utilized depending on the desired applicationof the device, the illustrated shape being a typical shape for treatinga linear incision.

The patch 10 then further includes a return or counter electrode chamber16 containing a return or counter electrode 18. A source of electriccurrent is provided which may be a lithium cell as at 20 or any othersuitable device. As an alternative, a galvanic couple may be provided aspart of the electrode composition which can supply a relatively constantcurrent for a relatively long time. For example, a galvanic couplehaving an anode constructed of zinc with a cathode constructed ofAg/AgCl will provide a 1-volt power supply. Current control is optionalbut preferred, and may be provided as by a resistor, transistor or otherelectronic current device 22, as is well known in the art, and theelements are connected together in a circuit as by conductive connectors24, 26, 28. The full circuit is completed when the patch is applied tothe skin of a patient in a well known manner. A covering layer oroverlay membrane is shown at 30 which is provided with an anestheticcoating to adhere the patch 10 to the skin of a user.

FIG. 2 a depicts a schematic sectional view through a patch 40 as itappears attached to the skin of a patient. The patch 40, services topatch 10, includes a donor electrode chamber 42 containing a donorelectrode 44 and containing an amount of anesthetic agent 46 carried byan absorbent pad 48. The absorbent pad 48 includes an amount of materialextending beyond the area occupied by the anesthetic agent at 46 whichmay be utilized to absorb material weeping from a wound or incision intothe patch. Such a wound or incision is illustrated by 50. A coveringmember layer is shown at 52 which adheres the patch 40 to skin 54 as bya peripheral adhesive layer 56 which also serves to save the patch andprevent leakage from the wound or incision beyond the patch.

FIG. 2 b depicts an alternate embodiment 60 in which a separate orexpansion portion of the donor or delivery chamber 62 is provided at 64and is in communication with the main donor or delivery chamber 62through a slotted opening as at 66. The delivery chamber 62 is otherwisefilled by the material containing an amount of the anesthetic agent tobe delivered at 68, the absorbent material in the expansion chamber 64being utilized to accommodate weepage material from a correspondingwound or incision 50 to be treated. A donor delivery electrode is shownat 70 and a covering layer 72 is shown peripherally adhering the device60 to the skin 54 using an adhesive as at 74.

FIG. 3 depicts a different embodiment of a patch device 80 including adelivery or donor chamber 82 filled with an absorbent materialcontaining an amount of an anesthetic agent 84 and a delivery or donorelectrode is shown as at 86. The material 84 is one which expands orswells as it takes on or absorbs additional liquid in the form ofweepage material from wound or incision 50 and has a relatively largecapacity for liquid. The device includes a covering layer 88 whichincludes an expandable or stretchable area, which may be an elasticband, which enables it to expand as at 90, as shown by the arrow 92.Adhesive holds the device in place on the skin of a patient as at 94.

The preferred anesthetic agents to be delivered include lidocaine,bupivicaine, ropivicaine and mepivicaine. These agents are normallyprovided in a water solution which is readily absorbed in a delivery padwhich is preferably made from or includes an amount of a natural orsynthetic fibrous material which is relatively inert to the materials itcontacts and the iontophoresis process. The electrodes utilized in theiontophoresis patch itself may be selected from known donor and returnor counter electrodes. Typically, the donor electrode may be zinc orsilver and the counter electrode may be silver chloride for positivelycharged anesthetic ions. While many batteries or other sources of AMF todrive the iontophoresis of the patch may be provided, button-typelithium cells have been successfully used.

The results of certain examples are displayed in FIGS. 4 and 5 and thesewill next be presented.

EXAMPLE 1 In-Vitro Delivery of Lidocaine into an Incision Using HumanCadaver Skin

An incision was made in cadaver skin, which was then sutured closed. Adelivery chamber consisting of an absorbent pad saturated with 4%lidocaine was placed over the incision. A zinc donor electrode wasconnected to the 4 cm² delivery pad, and a silver chloride counterelectrode was placed in a location remote to the delivery chamber, inionic contact with the cadaver skin by an agarose gel filled with 0.9%saline. To determine whether lidocaine is transferred by iontophoresis,several microdialysis probes were placed in varying locations: under theincision, under the dermis adjacent to the incision, and into an agarosegel at 1 and 4 cm depths underlying the cadaver skin. Current wasincreased from 0.12 mA for the first two hours to 0.33 mA in hours 2-4and to 0.54 mA in hours 4-6. As a passive control, the same apparatuswas used absent current flow. Concentration of lidocaine sufficient tocause anesthesia was generated in the incision, at all current densitiestested. The results of this study are shown in plot form in FIG. 4.

As can be seen from FIG. 4, the use of the iontophoresis patch of theinvention accomplishes an approximate four-fold increase in the activematerial actually reaching the incision where it can administeranesthetic effects. In addition, excellent current flow through theincision is accomplished as also shown by the data in FIG. 4.

EXAMPLE 2 n-Vivo Delivery of Lidocaine into Surgically RepairedIncisions

An incision was made in hairless rats, which was then sutured closed. Adelivery chamber, consisting of an absorbent pad saturated with 4%lidocaine, was placed over the incision. A silver donor electrode wasconnected to the 2 cm² delivery pad and a silver chloride counterelectrode chamber filled with 0.9% saline was placed on the animal in alocation remote to the delivery chamber. To determine whether lidocaineis transferred by iontophoresis, a microdialysis probe was placed in theincision. A total of 0.3 mA of iontophoretic current was applied for 24hours, with lidocaine concentration monitored within the incision. As apassive control, the same apparatus was used absent current flow.Concentration of lidocaine sufficient to cause anesthesia was generatedin the incision for the entire 24-hour period for the activeiontophoretic probe. The results of this study are shown in plot form inFIG. 5.

While the present invention is particularly useful for delivery ofanesthetic agents, those skilled in the art will recognize that use inother applications is certainly possible. For example, the patches maybe used for the delivery of anti-microbial compounds such as silver ion,gentamicin, ampicillin, or kanamycin to prevent infection in open woundsduring the healing process.

It will also be recognized that non-ionic compounds may be deliveredusing a patch in accordance with the present invention throughelectro-osmosis. Examples of useful non-ionic compounds may beanti-microbial compounds such as benzyl alcohol or anti-acne agents suchas benzoyl peroxide.

Patches in accordance with the invention may also be used to deliveryanti-acne compounds such as salicylate derivatives into acne lesions,which can become open skin wounds as acne changes from papules topustules.

One embodiment of a patch suitable for the delivery of agents to treatacne lesions is illustrated in FIG. 6. The patch, generally at 100,includes an anode chamber 102, the contents of which are in electricalcommunication with an amount of anode electrode material at 104. Theanode material may preferably include zinc. The anode chamber 102further houses an absorbent patch or gel material 106 as has beendescribed above suitable for retaining an amount of an ionic species. Anamount of open space 108 is provided in the chamber 102 to accommodateweepage liquid from adjacent lesions. The patch 100 further includes acathode chamber 110 containing material in electrical communication withan amount of cathode electrode material which may preferably besilver/silver chloride (Ag/AgCl) as at 112. An amount of absorbentmaterial for containing a solution or gel containing a cathode-deliveredionic species is shown at 114 and a peripheral weepage collection spaceis shown at 116. The electrodes 104 and 112 are connected by a conductor118 and a current regulating device may optionally also be provided inthe circuit (not shown).

When the active agent is negatively charged (such as with salicylateion), it is preferably placed in the cathode chamber. When the activeagent is positively charged (such as with silver ion) or neutral (suchas with benzyl alcohol), it is preferably placed in the anode chamber.Whichever chamber contains the active agent is to be placed over thetreatment area of skin. The acne patch is typically somewhat smaller insize than an incision patch and one embodiment was about 0.875 inch(2.22 cm) wide by 1.84 inches (4.69 cm) long.

It will be appreciated that the iontophoretic patches of the inventionmay be provided with the active agent to be delivered contained andstored in the patch or an agent may be separately provided forincorporation at the time of use. The active agent may also be containedin the patch but stored isolated from the electrodes and from the powersource during storage prior to use. In this type of patch, the gel orsolution containing the active agent is contacted with the deliverysystem when the patch is activated. Such a system is shown and describedin Anderson et al. (U.S. Pat. No. 6,745,071) which is assigned to thesame assignee as the present invention and which is deemed incorporatedby reference herein in its entirely for any purpose.

This invention has been described herein in considerable detail in orderto comply with the patent statutes and to provide those skilled in theart with the information needed to apply the novel principles and toconstruct and use embodiments of the example as required. However, it isto be understood that the invention can be carried out by specificallydifferent devices and that various modifications can be accomplishedwithout departing from the scope of the invention itself.

1. A transdermal system for the delivery of an anesthetic agent directlyto a selected site of an open skin wound by iontophoresis comprising:(a) a transdermal skin-worn patch including a donor electrode chambercontaining a donor electrode and a medium for containing an amount ofanesthetic agent in a form suitable for transdermal delivery inelectrical communication with said donor electrode, said patch furthercomprising a return electrode; (b) a source of electric currentconnected in a circuit with said donor and return electrodes; (c)wherein said donor electrode chamber includes a provision for absorbinga quantity of fluid associated with weepage from adjacent injured skintissue.
 2. A transdermal system as in claim 1 further comprising anamount of anesthetic agent in said patch.
 3. A transdermal system as inclaim 1 wherein said anesthetic agent is selected from lidocaine,bupivicaine, ropivicaine and mepivicaine.
 4. A transdermal system as inclaim 2 wherein said anesthetic agent is selected from lidocaine,bupivicaine, ropivicaine and mepivicaine.
 5. A transdermal system as inclaim 1 having a delivery output ≦ to 0.15 mA/cm² to the skin of apatient.
 6. A transdermal system as in claim 1 that delivers medicationover a period of at least thirty minutes.
 7. A transdermal system as inclaim 6 that delivers medication over a period of at least two hours. 8.A transdermal system as in claim 1 wherein the circuit includes acurrent regulating device in said circuit for controlling the electricaloutput of said patch, and current is maintained at <0.10 mA/cm².
 9. Atransdermal system as in claim 4 wherein said anesthetic agent islidocaine.
 10. A transdermal system as in claim 1 wherein said donorelectrode chamber is one of fixed volume that incorporates an absorbentpad for containing said anesthetic agent that has additional capacity toabsorb a quantity of weepage fluid.
 11. A transdermal system as in claim1 wherein said donor electrode chamber includes a pad for containingsaid anesthetic agent and includes an expansion chamber in communicationtherewith that includes an absorbent pad that provides additionalcapacity to absorb a quantity of weepage fluid.
 12. A transdermal systemas in claim 1 comprising an expanding donor electrode chamber isprovided with an absorbent pad for containing said anesthetic agent,said pad having additional capacity to absorb a quantity of weepagefluid while expanding the volume of said donor electrode chamber.
 13. Atransdermal system as in claim 2 wherein said anesthetic agent iscontained in a water-based solution.
 14. A transdermal system as inclaim 2 wherein said anesthetic agent is contained in the form of agelled material.
 15. A transdermal system as in claim 14 wherein saidgel comprises hydroxypropylmethylcellulose (HPMC).
 16. A transdermalsystem as in claim 1 wherein said provision for absorbing fluid includesan absorbent pad.
 17. A transdermal system as in claim 16 wherein saidabsorbent pad comprises natural or synthetic fibrous material.
 18. Atransdermal system for the delivery of an ionic therapeutic agentdirectly to a selected site of an open skin wound by iontophoresiscomprising: (a) a transdermal skin-worn patch including a donorelectrode chamber containing a donor electrode and an amount oftherapeutic agent in a form suitable for transdermal delivery inelectrical communication with said donor electrode, said patch furthercomprising a return electrode; (b) a source of electric currentconnected in a circuit with said donor and return electrodes; and (c)wherein said donor electrode chamber includes a provision for absorbinga quantity of fluid associate with weepage from adjacent injured skintissue.
 19. A transdermal system as in claim 18 wherein said ionic agentis selected from the group consisting of anti-microbial and anti-acneagents.
 20. A transdermal system as in claim 18 wherein said ionictherapeutic agent is an anti-acne agent.
 21. A method of administeringan ionic therapeutic agent directly to a selected site of an open skinwound comprising: causing a skin-worn patch as in claim 18 to bepositioned over a selected skin site, the donor electrode chamber placedover the desired treatment area.